1. Field of the Invention
The present invention relates to the field of mass spectrometry, and more particularly to a mass spectrometer system and method that provides for one or more data dependent decisions to be made as to altering scan parameters based upon information acquired during the scan.
2. Discussion of the Related Art
Data dependent experiments currently involve collecting a mass spectral scan and then performing one or more subsequent scans based upon the analysis of data in the first scan. Generally described, data-dependent acquisition involves using data derived from an experimentally-acquired mass spectrum in an “on-the-fly” manner to direct the subsequent operation of a mass spectrometer; for example, a mass spectrometer may be switched between MS and MS/MS scan modes upon detection of an ion species of potential interest. Utilization of data-dependent acquisition methods in a mass spectrometer provides the ability to make automated, real-time decisions in order to maximize the useful information content of the acquired data. Current systems and methods that provide for real time data dependent functionality include, but are not limited to: the Data Dependent Experiment™ (DDE) tool utilized by Thermo Finnigan LLC of San Jose, Calif., the Data Directed Analysis (DDA) tool by Waters Corporation (Micromass™) and the Information Dependant Acquisition™ (IDA™) system marketed by MDS Sciex Inc. and Applera Corporation.
Data-dependent acquisition methods may be characterized as having one or more input criteria, and one or more output actions. The input criteria employed for conventional data-dependent methods are generally based on parameters such as intensity, intensity pattern, mass window, mass difference (neutral loss), mass-to-charge (m/z) inclusion and exclusion lists, and product ion mass. The input criteria are employed to select one or more ion species that satisfy the criteria. The selected ion species are then subjected to an output action (examples of which include performing MS/MS or MS” analysis and/or high-resolution scanning). In one instance of a typical data-dependent experiment, a group of ions are mass analyzed, and precursor ion species having mass spectral intensities exceeding a specified threshold are subsequently selected as precursor ions for MS/MS analysis, which may involve operations of isolation, dissociation of the precursor ions, and mass analysis of the product ions.
Generally, a mass spectrometer configured to provide such data dependent analysis most often includes: an ion source to transform introduced molecules in a sample into ionized fragments; an analyzer to separate such ionized ions by their masses by applying electric and magnetic fields; and a detector to measure and thus provide data for identifying and calculating the abundances of each ion fragment present. Moreover, such a mass spectrometer system often can and does include a two-dimensional (2D) and/or a three-dimensional (3D) ion trap that enables the storage of ions over a large range of masses for relatively large periods of time. Once the ions are formed and stored, various known techniques can be performed for isolating the desired ions of interest and for conducting MS/MS or (MS)n experiments. In particular, MS/MS often involves fragmentation of an ion or ions of interest in order to obtained desired information regarding the one or more ions' structure.
The fragmentation process itself typically includes the use of an auxiliary voltage of low amplitude (e.g., up to about 20 volts at a duration of up to about tens of milliseconds) configured with a resonance frequency to match desired ions frequencies of motion, which in turn is determined by the main trapping RF field amplitude and the ions mass-to-charge ratio (m/z). Particular ions in resonance with such an auxiliary applied voltage take up the energy and their amplitude of motion grows. In an ideal quadrupole field, the amplitude of resonating ions grows linearly with time if the resonance voltage is continuously applied. As the amplitude increases, the kinetic energy of resonating ions also increases (i.e., as the square of the amplitude) and thus any collisions that occur with introduced neutral gas molecules or other ions become increasingly energetic. Eventually, the collisions which occur deposit enough energy into the molecular bonds of the resonating ions to cause bonds to break and thus cause fragmentation. The beneficial result of such a method is a desired mass spectrum for analysis.
However, a constraint that has continued to limit mass spectrometer apparatus that utilize such 2D and 3D ion trap mass analyzer instruments is that upon initiating a scan of the contents of the traps, a completion of the initiated scan may be unwarranted based upon information that is obtained during scanning. In particular, there are no commercially available systems in place to direct such a system to automatically stop an MS, (MS)n or MS/MS scan in progress or continue such scans based on interrogated (m/z) data provided during the scan itself.
Background information on a data dependent system that alternates between a fast scan (i.e., measurement scan) and a slow scan (i.e., a survey scan) based on a pre-scan map, is described and claimed in U.S. Pat. No. 4,837,434, entitled, MASS SPECTROMETRY SYSTEM AND METHOD EMPLOYING MEASUREMENT/SURVEY SCAN STRATEGY,” issued Jun. 6, 1989, to James, including the following, “A gas chromatography plus mass spectrometry system implements a scan strategy in which each full range scan alternates between a normal measurement mode and a survey mode based on a block/gap map made during the previous scan. Survey mode is used within regions that were determined in the previous scan to lack signal above a predetermined threshold. Spectral data is generated during measurement mode operation. Each scan serves both measurement and mapping functions in a way that avoids mass filter jumps, since each scan is monotonic over the entire scanning range.”
Background information for a data dependent mass spectrometer system that enables peptidic analysis, is described and claimed in U.S. Pat. No. 7,498,568, entitled, “REAL-TIME ANALYSIS OF MASS SPECTROMETRY DATA FOR IDENTIFYING PEPTIDIC DATA OF INTEREST,” filed Apr. 29, 2005, to Overney et al., including the following, “A mass spectrometry system is described. The mass spectrometry system comprises: (a) a mass spectrometer; and (b) a controller connected to the mass spectrometer. The controller is configured to: (i) direct the mass spectrometer to acquire a precursor ion spectrum of a sample stream; (ii) analyze, in real-time, the precursor ion spectrum to determine whether a first evaluation criterion is satisfied; (iii) if the first evaluation criterion is satisfied, direct the mass spectrometer to acquire a product ion spectrum of the sample stream; (iv) analyze, in real-time, the product ion spectrum to determine whether a second evaluation criterion is satisfied; and (v) if the second evaluation criterion is satisfied, analyze the product ion spectrum to assign an identification to the product ion spectrum. For certain implementations, the controller allows automated, data-dependent acquisition of mass spectrometry data to improve the efficiency at which peptidic data of interest can be acquired.”
Background information for a data dependent mass spectrometer system that provides for selection of various dissociation techniques, is described and claimed in PCT application WO/2008/025014 A2, entitled, “DATA-DEPENDENT SELECTION OF DISSOCIATION TYPE IN A MASS SPECTROMETER,” published filed Aug. 25, 2006, to Schwartz et al., including the following, “Methods and apparatus for data-dependent mass spectrometric MS/MS or MSn analysis are disclosed. The methods may include determination of the charge state of an ion species of interest, followed by automatic selection (e.g., CAD, ETD, or ETD followed by a non-dissociative charge reduction or collision activation) based at least partially on the determined charge state. The ion species of interest is then dissociated in accordance with the selected dissociation type, and an MS/MS or MSn spectrum of the resultant product ions may be acquired.”
Accordingly, a need exists for a mass spectrometer system that utilizes a data dependent method of altering the acquisition of a given scan by monitoring for ion species of interest during the scan so as to determine whether to continue or terminate the present scan in order to preserve overall cycle time and improve efficiency. The present invention is thus directed to such a need.